Table 2. Categories of mastocytosis and corresponding type of KIT mutations.

Type of Mastocytosis	Prognosis	Treatment options	Type/frequency of KIT and other genetic lesions
Pediatric mastocytosis (PM)	Very Good	Most cases regress with age	25% KIT WT 35% KIT D816V/I/Y 40% ECD KIT mutations
Indolent mastocytosis (ISM)	Very good to good	No cytoreductive therapy necessary	> 80% KIT D816V mutations
Smoldering systemic mastocytosis (SSM)	Relatively good	‘Wait and watch’ in most cases, some may require Interferon (IFN), glucocorticosteriods and cladribine (2CdA)	> 80% KIT D816V mutations Additional non-KIT mutations acquired over disease progression
Aggressive systemic mastocytosis (ASM)	Poor	IFN, 2CdA; resistant forms treated with TKIs/chemotherapy/hydroxyurea	> 60% KIT D816V mutations Few non-codon 816 KIT mutations Additional non-KIT mutations (D820G, V559I)
Systemic mastocytosis with associated non-hematological MC disease (SM-AHNMD)	Depending on the type of SM and prognosis of associated AHNMD	Imatinib to control AHNMD; for SML-AML and aggressive types chemotherapy followed by allogenic stem cell transplantation	> 80% KIT D816V mutations AHNMD presents with genetic lesions Non-KIT mutations
Mast cell leukemia/Mast cell sarcoma (MCL/MCS)	Very poor	Polychemotherapy, allogenic stem cell transplantation, 2CdA, TKIs, Hydroxyurea	MCL: KIT D816V is least (46%) KIT ECD, JMD mutations No KIT mutation (WT KIT) MCS: No KIT D816V mutation till date (N822K, del419 found)
Familial mastocytosis	Usually good	Imatinib and TKIs	Rare somatic KIT D816V mutations Germline mutation or deletions (K509I, A533D, R634W, N821I, M835K, S849I or del419, del559-560)

Adapted and compiled from Peter Valent, Mastocytosis: a paradigmatic example of a rare disease with complex biology and pathology, Am J Can Res 2013; 3;159–172; and from M. Arock et al, KIT mutation analysis of mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis, Leukemia 2015, 1–10